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海洋环肽stylissamide Ⅰ的全合成研究

陆东涛,  刘超,  秦路平,  邹燕

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文章导航 > 药学实践与服务  > 2019 >  37(5): 444-449
陆东涛, 刘超, 秦路平, 邹燕. 海洋环肽stylissamide Ⅰ的全合成研究[J]. 药学实践与服务, 2019, 37(5): 444-449. doi: 10.3969/j.issn.1006-0111.2019.05.011
引用本文: 陆东涛, 刘超, 秦路平, 邹燕. 海洋环肽stylissamide Ⅰ的全合成研究[J]. 药学实践与服务, 2019, 37(5): 444-449. doi: 10.3969/j.issn.1006-0111.2019.05.011
shu
LU Dongtao, LIU Chao, QIN Luping, ZOU Yan. The total solid synthesis of marine cyclopeptide stylissamide Ⅰ[J]. Journal of Pharmaceutical Practice and Service, 2019, 37(5): 444-449. doi: 10.3969/j.issn.1006-0111.2019.05.011
Citation: LU Dongtao, LIU Chao, QIN Luping, ZOU Yan. The total solid synthesis of marine cyclopeptide stylissamide Ⅰ[J]. Journal of Pharmaceutical Practice and Service, 2019, 37(5): 444-449. doi: 10.3969/j.issn.1006-0111.2019.05.011
shu

海洋环肽stylissamide Ⅰ的全合成研究

doi: 10.3969/j.issn.1006-0111.2019.05.011
  • 1.

    海军军医大学长海医院 药材科, 上海 200433

  • 2.

    海军军医大学 药学院, 上海 200433

基金项目: 海军军医大学军事课题（2017JS11）

The total solid synthesis of marine cyclopeptide stylissamide Ⅰ

  • 1.

    Department of Pharmacy, Changhai Hospital, Naval Medical University, Shanghai 200433, China

  • 2.

    School of Pharmacy, Naval Medical University, Shanghai 200433, China

  • 摘要: 目的 采用固相合成/液相环化方法合成海洋环肽stylissamide Ⅰ。 方法 以2-氯三苯甲基氯树脂（简称二氯树脂）为载体，选用6-氯苯并三氮唑-1，1，3，3-四甲基脲六氟磷酸酯（HCTU）和N，N-二异丙基乙胺（DIPEA）为缩合试剂依次连接9-笏甲氧羰基保护的氨基酸，在三氟乙醇（TFE）的作用下将直链肽从树脂上切割下来，然后使用（3H-1，2，3-三唑并吡啶-3-氧基）三-1-吡咯烷基六氟磷酸盐（PyAOP），N-羟基-7-氮杂苯并三氮唑（HOAt）和N-甲基吗啡啉（NMM）在溶液中完成环合，最后在三氟乙酸（TFA）的处理下脱去侧链保护基，获得环肽粗品。经反相高效液相色谱对所合成的环肽粗品进行纯化，终产物纯度98.9%。通过高分辨质谱、600 MHz 1H-NMR和13C-NMR鉴定，确定所合成环肽为目标环肽。 结果 首次完成海洋环肽stylissamide Ⅰ的全合成，总收率为67%。 结论 此法具有快捷、简便、高效的特点，较好地为stylissamide Ⅰ的固相全合成提供了参考。
    Abstract: Objective The marine cyclopeptide stylissamide Ⅰ was synthesized through a solid phase synthesis and cyclization in solution(SPS-CS). Methods 2-chlorotrityl chloride resin was used as solid support for the total synthesis.Each amino acid protected by 9-fluorenylmethyloxycarbonyl(Fmoc) group was coupled with N,N-diisopropylethylamine(DIPEA)/O-(6-chloro-1-hydrocibenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluoro- phosphat(HCTU) as condensing agents.The linear peptide was cleaved from resin by 2,2,2-trifluoroethanol(TFE) and cyclized in the presence of(7-azabenzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate(PyAOP)/1-hydroxy-7-azabenzotriazole(HOAt)/N-methyl morphofine(NMM).Finally,the crude cyclopeptide was obtained through global deprotection with trifluoroacetic acid(TFA).The target compound was purified by preparative RP-HPLC to 98.9% pure and its structure was identified by 1H-NMR,13C-NMR and Q-TOF LC/MS. Results The first total synthesis of the marine cyclopeptide stylissamide Ⅰ was successfully realized with a yield of 67%. Conclusion A rapid,simple and high-efficient method of stylissamide Ⅰ total synthesis was successfully established.
  • [1] NORO J C,KALAITZIS J A,NEILAN B A.Bioactive natural products from Papua New Guinea marine sponges[J].Chem Biodivers,2012,9(10):2077-2095.
    [2] PROKSCH P,EBEL R,EDRADA R A,et al.Bioactive natural products from marine invertebrates and associated fungi[J].Prog Mol Subcell Biol,2003,37:117-142.
    [3] ANDAVAN G S,LEMMENS-GRUBER R.Cyclodepsipeptides from marine sponges:Natural agents for drug research[J].Mar Drugs,2010,8(3):810-834.
    [4] PIFFERI C,BERTHET N,RENAUDET O.Cyclopeptide scaffolds in carbohydrate-based synthetic vaccines[J].Biomater Sci,2017,5(5):953-965.
    [5] KURANAGA T,SESOKO Y,INOUE M.Cu-mediated enamide formation in the total synthesis of complex peptide natural products[J].Nat Prod Rep,2014,31(4):514-532.
    [6] RUSSO A,AIELLO C,GRIECO P,et al.Targeting "undruggable" proteins:design of synthetic cyclopeptides[J].Curr Med Chem,2016,23(8):748-762.
    [7] DAHIYA R,GAUTAM H.Toward the synthesis and biological screening of a cyclotetrapeptide from marine bacteria[J].Mar Drugs,2010,9(1):71-81.
    [8] CHANDRA K,ROY T K,SHALEV D E,et al.A tandem in situ peptide cyclization through trifluoroacetic acid cleavage[J].Angew Chem Int Ed Engl,2014,53(36):9450-9455.
    [9] DALETOS G,KALSCHEUER R,KOLIWER-BRANDL H,et al.Callyaerins from the marine sponge Callyspongia aerizusa:Cyclic peptides with antitubercular activity[J].J Nat Prod,2015,78(8):1910-1925.
    [10] ZHOU X,HUANG H,CHEN Y,et al.Marthiapeptide A,an anti-infective and cytotoxic polythiazole cyclopeptide from a 60 L scale fermentation of the deep sea-derived Marinactinospora thermotolerans SCSIO 00652[J].J Nat Prod,2012,75(12):2251-2255.
    [11] KANG K B,MING G,KIM G J,et al.Jubanines F-J,cyclopeptide alkaloids from the roots of Ziziphus jujuba[J].Phytochemistry,2015,119:90-95.
    [12] ESMAEILI M A,ABAGHERI-MAHABADI N,HASHEMPOUR H,et al.Viola plant cyclotide vigno 5 induces mitochondria-mediated apoptosis via cytochrome C release and caspases activation in cervical cancer cells[J].Fitoterapia,2016,109:162-168.
    [13] THEVENARD J,RAMONT L,DEVY J,et al.The YSNSG cyclopeptide derived from tumstatin inhibits tumor angiogenesis by down-regulating endothelial cell migration[J].Int J Cancer,2010,126(5):1055-1066.
    [14] FESTA C,DE MARINO S,SEPE V,et al.Solomonamides A and B,new anti-inflammatory peptides from Theonella swinhoei[J].Org Lett,2011,13(6):1532-1535.
    [15] SONG L,WANG Z,WANG Y,et al.Natural Cyclopeptide RA-XⅡ,a new autophagy inhibitor,suppresses protective autophagy for enhancing apoptosis through AMPK/mTOR/P70S6K pathways in HepG2 cells[J].Molecules,2017,22(11):1934.
    [16] SCHMIDT G,GRUBE A,KÖCK M.Stylissamides A-D new proline-containing cyclic heptapeptides from the marine sponge Stylissa caribica[J].Eur J Org Chem,2007,2007(24):4103-4110.
    [17] CYCHON C,KÖCK M.Stylissamides E and F,cyclic heptapeptides from the caribbean sponge Stylissa caribica[J].J Nat Prod,2010,73(4):738-742.
    [18] CYCHON C,SCHMIDT G,KÖCK M.Sequencing of cyclic peptides by NMR and MS techniques demonstrated on stylissamides A-F[J].Phytochem Rev,2013,12(3):495-505.
    [19] KUBOTA T,KOBAYASHI J,NAKAMURA K,et al.stylissamide Ⅰ,a new cyclic heptapeptide from an okinawan marine sponge Stylissa sp.[J].Heterocycles,2017,95(2):799-806.
    [20] 刘雷明,王国亮,王建华,等.AoGDW肽固相合成工艺研究[J].化学试剂,2009,31(11):871-874.
    [21] RIJKERS D T S,KRUIJTZER J A W,KILLIAN J A,et al.A convenient solid phase synthesis of S-palmitoyl transmembrane peptides[J].Tetrahedron Lett,2005,46(19):3341-3345.
    [22] CHEN Y,LIU C,LIU N,et al.Total synthesis and antibacterial study of cyclohexapeptides desotamide B,wollamide B and their analogs[J].Chem Biodivers,2017,15(1):e1700414.
    [23] LIU C,ZOU Y,SONG H,et al.Arylboronate ester protected amino acids as orthogonal building blocks for fmoc solid phase peptide synthesis[J].Eur J Org Chem,2017,2017(39):5916-5920.
    [24] HUMPHREY J M,CHAMBERLIN A R.Chemical synthesis of natural product peptides:coupling methods for the incorporation of non-coded amino acids into peptides[J].Chem Rev,1997,97(6):2243-2266.
    [25] LIU C,CHEN X,ZHI X,et al.Structure-based development of an osteoprotegerin-like glycopeptide that blocks RANKL/RANK interactions and reduces ovariectomy-induced bone loss in mice[J].Eur J Med Chem,2018,145:661-672.
    [26] HU H,XUE J,SWARTS B M,et al.Synthesis and antibacterial activities of N-glycosylated derivatives of tyrocidine A,a macrocyclic peptide antibiotic[J].J Med Chem,2009,52(7):2052-2059.
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  • 收稿日期:  2018-10-31
  • 修回日期:  2019-02-13

海洋环肽stylissamide Ⅰ的全合成研究

doi: 10.3969/j.issn.1006-0111.2019.05.011
  • 1. 海军军医大学长海医院 药材科, 上海 200433
  • 2. 海军军医大学 药学院, 上海 200433
    • 基金项目:  海军军医大学军事课题（2017JS11）
  • 收稿日期: 2018-10-31
  • 修回日期: 2019-02-13

摘要: 目的 采用固相合成/液相环化方法合成海洋环肽stylissamide Ⅰ。 方法 以2-氯三苯甲基氯树脂（简称二氯树脂）为载体，选用6-氯苯并三氮唑-1，1，3，3-四甲基脲六氟磷酸酯（HCTU）和N，N-二异丙基乙胺（DIPEA）为缩合试剂依次连接9-笏甲氧羰基保护的氨基酸，在三氟乙醇（TFE）的作用下将直链肽从树脂上切割下来，然后使用（3H-1，2，3-三唑并吡啶-3-氧基）三-1-吡咯烷基六氟磷酸盐（PyAOP），N-羟基-7-氮杂苯并三氮唑（HOAt）和N-甲基吗啡啉（NMM）在溶液中完成环合，最后在三氟乙酸（TFA）的处理下脱去侧链保护基，获得环肽粗品。经反相高效液相色谱对所合成的环肽粗品进行纯化，终产物纯度98.9%。通过高分辨质谱、600 MHz 1H-NMR和13C-NMR鉴定，确定所合成环肽为目标环肽。 结果 首次完成海洋环肽stylissamide Ⅰ的全合成，总收率为67%。 结论 此法具有快捷、简便、高效的特点，较好地为stylissamide Ⅰ的固相全合成提供了参考。

English Abstract

陆东涛, 刘超, 秦路平, 邹燕. 海洋环肽stylissamide Ⅰ的全合成研究[J]. 药学实践与服务, 2019, 37(5): 444-449. doi: 10.3969/j.issn.1006-0111.2019.05.011
引用本文: 陆东涛, 刘超, 秦路平, 邹燕. 海洋环肽stylissamide Ⅰ的全合成研究[J]. 药学实践与服务, 2019, 37(5): 444-449. doi: 10.3969/j.issn.1006-0111.2019.05.011
shu
LU Dongtao, LIU Chao, QIN Luping, ZOU Yan. The total solid synthesis of marine cyclopeptide stylissamide Ⅰ[J]. Journal of Pharmaceutical Practice and Service, 2019, 37(5): 444-449. doi: 10.3969/j.issn.1006-0111.2019.05.011
Citation: LU Dongtao, LIU Chao, QIN Luping, ZOU Yan. The total solid synthesis of marine cyclopeptide stylissamide Ⅰ[J]. Journal of Pharmaceutical Practice and Service, 2019, 37(5): 444-449. doi: 10.3969/j.issn.1006-0111.2019.05.011
shu

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